The aryl hydrocarbon receptor is a novel negative regulator of interleukin‐17‐mediated signaling and inflammation in vitro
2019
Li, Hui | Hong, Wei | Jin, Xiangyu | Li, Guangliang | Zhou, Guoming | Fan, Liping
Interleukin (IL)‐17 plays a critical role in the pathogenesis of inflammation and autoimmune diseases. The aryl hydrocarbon receptor (AHR) is a transcription factor responsible for the elimination of xenobiotic chemicals. However, it remains unknown whether AHR is involved in IL‐17 signaling. Here, we demonstrate that knockdown of AHR significantly enhances, while overexpression or activation of AHR inhibits IL‐17‐induced inflammation in Hela cells. AHR specifically suppresses IL‐17‐induced p38 activation, and inhibition of p38 activity markedly reverses the effect of AHR knockdown on IL‐17‐induced inflammation. Mechanistically, AHR physically interacts with TAK1 and mitogen‐activated protein kinase kinase 3/6 (MKK3/6) and disrupts TAK1‐MKK3/6 interaction, leading to impaired IL‐17 signaling. Thus, our study indicates that AHR negatively regulates IL‐17‐mediated signaling and inflammation at least partially through interfering with the interaction between TAK1 and MKK3/6.
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